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Article ; Online: In Vitro and In Vivo Effects of IGF-1 Delivery Strategies on Tendon Healing: A Review.

Miescher, Iris / Rieber, Julia / Calcagni, Maurizio / Buschmann, Johanna

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors ... ...

Abstract	Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors have been under view for decades. Insulin-like growth factor-1 (IGF-1) is one of the used growth factors and has been applied to tenocyte in vitro cultures as well as in animal preclinical models and to human patients due to its anabolic and matrix stimulating effects. In this narrative review, we cover the current literature on IGF-1, its mechanism of action, in vitro cell cultures (tenocytes and mesenchymal stem cells), as well as in vivo experiments. We conclude from this overview that IGF-1 is a potent stimulus for improving tendon healing due to its inherent support of cell proliferation, DNA and matrix synthesis, particularly collagen I, which is the main component of tendon tissue. Nevertheless, more in vivo studies have to be performed in order to pave the way for an IGF-1 application in orthopedic clinics.
MeSH term(s)	Animals ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Tendons/metabolism ; Wound Healing ; Tendon Injuries/drug therapy ; Collagen Type I/metabolism
Chemical Substances	Insulin-Like Growth Factor I (67763-96-6) ; Collagen Type I
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032370
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Article ; Online: Transition metals in angiogenesis - A narrative review.

Dürig, Johannes / Calcagni, Maurizio / Buschmann, Johanna

Materials today. Bio

2023 Volume 22, Page(s) 100757

Abstract: The aim of this paper is to offer a narrative review of the literature regarding the influence of transition metals on angiogenesis, excluding lanthanides and actinides. To our knowledge there are not any reviews up to date offering such a summary, which ...

Abstract	The aim of this paper is to offer a narrative review of the literature regarding the influence of transition metals on angiogenesis, excluding lanthanides and actinides. To our knowledge there are not any reviews up to date offering such a summary, which inclined us to write this paper. Angiogenesis describes the process of blood vessel formation, which is an essential requirement for human growth and development. When the complex interplay between pro- and antiangiogenic mediators falls out of balance, angiogenesis can quickly become harmful. As it is so fundamental, both its inhibition and enhancement take part in various diseases, making it a target for therapeutic treatments. Current methods come with limitations, therefore, novel agents are constantly being researched, with metal agents offering promising results. Various transition metals have already been investigated in-depth, with studies indicating both pro- and antiangiogenic properties, respectively. The transition metals are being applied in various formulations, such as nanoparticles, complexes, or scaffold materials. Albeit the increasing attention this field is receiving, there remain many unanswered questions, mostly regarding the molecular mechanisms behind the observed effects. Notably, approximately half of all the transition metals have not yet been investigated regarding potential angiogenic effects. Considering the promising results which have already been established, it should be of great interest to begin investigating the remaining elements whilst also further analyzing the established effects.
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Review
ISSN	2590-0064
ISSN (online)	2590-0064
DOI	10.1016/j.mtbio.2023.100757
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Article ; Online: Delineation of the healthy rabbit duodenum by immunohistochemistry - A short communication.

Meier Bürgisser, Gabriella / Heuberger, Dorothea M / Giovanoli, Pietro / Calcagni, Maurizio / Buschmann, Johanna

Acta histochemica

2024 Volume 126, Issue 2, Page(s) 152136

Abstract: The duodenum acts as a vital organ that performs fundamental physiological functions like digestion and nutrient absorption. Situated in the lower abdomen, the duodenum is located between the stomach and the jejunum. Usually, the duodenum is divided into ...

Abstract	The duodenum acts as a vital organ that performs fundamental physiological functions like digestion and nutrient absorption. Situated in the lower abdomen, the duodenum is located between the stomach and the jejunum. Usually, the duodenum is divided into four anatomical portions. We here compare paraffin embedded and cryosections of the healthy rabbit duodenum for research purposes. This analysis evaluates the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting extracellular matrix markers collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and proliferation marker ki67 as well as inflammatory marker PAR-2. Subsequent recommendations are provided based on our findings. Furthermore, the advantage of an antigen retrieval step in immunohistochemical labelling of paraffin sections was demonstrated and confirmed with an isotype negative control. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labellings was performed in serial sections, showing that adjacent to the circular muscle of the duodenum, the connective tissue was composed of collagen I and fibronectin, while the artery and vein walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where particularly a type of gland adjacent to Brunner's glands showed prominent PAR-2 positive areas, while the Brunner's glands themselves were PAR-2 negative. Proliferating ki67 positive cells facing the lumen were highly abundant in all kinds of glands except for the Brunner's glands. This effort serves to furnish the research community with reference imagery pertinent to scientists opting for the rabbit duodenum model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rat intestinal tracts, or even offer insights into the human context.
MeSH term(s)	Humans ; Rabbits ; Animals ; Mice ; Rats ; Fibronectins ; Immunohistochemistry ; Ki-67 Antigen ; Duodenum ; Collagen Type I
Chemical Substances	Fibronectins ; Ki-67 Antigen ; Collagen Type I
Language	English
Publishing date	2024-01-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2024.152136
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Article ; Online: Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review.

Schneider, Isabelle / Calcagni, Maurizio / Buschmann, Johanna

Cytotherapy

2022 Volume 25, Issue 2, Page(s) 105–119

Abstract: Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin ... ...

Abstract	Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells.
MeSH term(s)	Humans ; Wound Healing ; Skin ; Adipocytes ; Adipose Tissue ; Stem Cells ; Skin Diseases/therapy
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2022.08.005
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Article ; Online: Delineation of the healthy rabbit tonsil by immunohistochemistry - A short communication.

Meier Bürgisser, Gabriella / Heuberger, Dorothea M / Giovanoli, Pietro / Calcagni, Maurizio / Buschmann, Johanna

Acta histochemica

2023 Volume 125, Issue 7, Page(s) 152098

Abstract: Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two oval protrusions in the wall of the oropharynx, the rabbit palatine tonsils are ... ...

Abstract	Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two oval protrusions in the wall of the oropharynx, the rabbit palatine tonsils are characterized by excretory ducts and trabeculae. We here compare paraffin embedded and cryosections of the healthy rabbit tonsils. This analysis centers on evaluating the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and ki67. Subsequent recommendations are provided based on our findings. Furthermore, we demonstrate the advantage of an antigen retrieval step in immunohistochemical labeling of paraffin sections. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labelings was furthermore performed in serial sections, showing that adjacent to the excretory ducts, the tonsillar tissue was particularly composed of collagen I and fibronectin, while the vessel walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where a small fraction of the cells found in the tonsillar connective tissue were PAR-2 positive (probably a subpopulation of mast cells), as well as the lumen of some excretory ducts and trabeculae. Collagen III on the other hand was only weakly expressed in the tonsils. Proliferating ki67 positive cells were rare. This endeavor serves to furnish the scientific community with reference imagery pertinent to researchers opting for the rabbit palatine tonsil model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rodent tonsils, or even offer insights into the human context.
MeSH term(s)	Humans ; Rabbits ; Animals ; Mice ; Palatine Tonsil/chemistry ; Immunohistochemistry ; Fibronectins ; Ki-67 Antigen ; Paraffin/analysis ; Collagen
Chemical Substances	Fibronectins ; Ki-67 Antigen ; Paraffin (8002-74-2) ; Collagen (9007-34-5)
Language	English
Publishing date	2023-10-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2023.152098
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Article: Impact of Electrospun Piezoelectric Core-Shell PVDFhfp/PDMS Mesh on Tenogenic and Inflammatory Gene Expression in Human Adipose-Derived Stem Cells: Comparison of Static Cultivation with Uniaxial Cyclic Tensile Stretching.

Baumgartner, Walter / Wolint, Petra / Hofmann, Silvan / Nüesch, Cléa / Calcagni, Maurizio / Brunelli, Marzia / Buschmann, Johanna

Bioengineering (Basel, Switzerland)

2022 Volume 9, Issue 1

Abstract: Specific microenvironments can trigger stem cell tenogenic differentiation, such as specific substrates or dynamic cell cultivation. Electrospun meshes composed by core-shell fibers (random or aligned; PDMS core; piezoelectric PVDFhfp shell) were ... ...

Abstract	Specific microenvironments can trigger stem cell tenogenic differentiation, such as specific substrates or dynamic cell cultivation. Electrospun meshes composed by core-shell fibers (random or aligned; PDMS core; piezoelectric PVDFhfp shell) were fabricated by coaxial electrospinning. Elastic modulus and residual strain were assessed. Human ASCs were seeded on such scaffolds either under static conditions for 1 week or with subsequent 10% dynamic stretching for 10,800 cycles (1 Hz, 3 h), assessing load elongation curves in a Bose
Language	English
Publishing date	2022-01-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering9010021
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Article ; Online: Delineation of the healthy rabbit heart by immunohistochemistry - A technical note.

Bürgisser, Gabriella Meier / Heuberger, Dorothea M / Schaffner, Nicola / Giovanoli, Pietro / Calcagni, Maurizio / Buschmann, Johanna

Acta histochemica

2022 Volume 125, Issue 1, Page(s) 151993

Abstract: Heart failure poses a big health problem and may result from obesity, smoking, alcohol and/or growing age. Studying pathological heart tissue demands accurate histological and immunohistochemical stainings in animal models, including chromogenic and ... ...

Abstract	Heart failure poses a big health problem and may result from obesity, smoking, alcohol and/or growing age. Studying pathological heart tissue demands accurate histological and immunohistochemical stainings in animal models, including chromogenic and fluorescent approaches. Moreover, a reliable set of healthy heart stainings and labeling are required, in order to provide a reference for the pathological situation. Heart and brain tissue of a healthy rabbit were collected, and different histological key steps were compared, such as paraffin embedding after formalin fixation versus cryopreservation; an antigen retrieval (AR) step in processing paraffin sections versus the same procedure without AR; or a chromogenic with a fluorescent detection system, respectively. Using serial sections, we stained the same morphological structure with classic approaches (HE, Masson Goldner Trichrome (GT) and Elastica van Gieson (EL)) and with different markers, including collagen I, collagen III, fibronectin, α-SMA, protease-activated receptor-2 (PAR-2) which is an inflammation-related marker, and ki67 for proliferating cells. Differences between conditions were quantitatively assessed by measuring the color intensity. Generally, cryosections exhibited a more prominent signal intensity in immunohistochemically labeled sections than in paraffin sections, but the strong staining was slurry, which sometimes impeded proper identification of morphological structures, particularly at higher magnifications. In addition, the advantage of an AR step was observed when compared to the condition without AR, where signal intensities were significantly lower. Different stainings of the heart arteries and the myocardium revealed a clear distribution of extracellular matrix components, with prominent collagen III in the artery wall, but an absence of collagen III in the myocardium. Moreover, paraffin-embedded sections provided more distinct structures compared to cryosections after collagen III, ki67, fibronectin, and α-SMA labeling. As for the Purkinje cells that were depicted in the heart and the cerebellum (Purkinje neurons), we found GT staining most suitable to depict them in the heart, while HE as well as EL staining was ideal to depict Purkinje neurons in the cerebellum. In sum, we provide useful reference images with different stainings for researchers using the rabbit heart or brain model. Such images can help to decide which of the immunohistochemical protocols are valuable to reach a specific aim. Recommendations are given for the best visualization of the target structures and specific (immunohistochemical) staining.
MeSH term(s)	Animals ; Rabbits ; Immunohistochemistry ; Fibronectins ; Ki-67 Antigen ; Paraffin ; Collagen ; Paraffin Embedding/methods
Chemical Substances	Fibronectins ; Ki-67 Antigen ; Paraffin (8002-74-2) ; Collagen (9007-34-5)
Language	English
Publishing date	2022-12-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2022.151993
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Article ; Online: Delineation of the healthy rabbit tongue by immunohistochemistry - A technical note.

Meier Bürgisser, Gabriella / Heuberger, Dorothea M / Rieber, Julia / Miescher, Iris / Giovanoli, Pietro / Calcagni, Maurizio / Buschmann, Johanna

Acta histochemica

2023 Volume 126, Issue 1, Page(s) 152127

Abstract: In the oral cavity the tongue is an important muscular organ that supports the swallowing of food and liquids. It is responsible for the sense of taste, based on the many different taste buds it contains. Research in the field of tongue diseases demands ... ...

Abstract	In the oral cavity the tongue is an important muscular organ that supports the swallowing of food and liquids. It is responsible for the sense of taste, based on the many different taste buds it contains. Research in the field of tongue diseases demands for suitable preclinical models. The healthy rabbit tongue may therefore serve as baseline and reference for the pathological situation. With this consideration, we covered the fixation and histological stainings as well as the immunohistochemical labelling of the healthy rabbit tongue. In this technical note, initial choice of the fixative is discussed, with a comparison of formalin fixation and subsequent paraffin embedding versus cryopreservation. Moreover, we delineate the effect of an antigen retrieval step for formalin fixation by several examples. Finally, we provide ECM markers collagen I, collagen III, fibronectin, α-SMA and elastin staining as well as ki67 for proliferative status and PAR-2 protein expression as a marker for inflammatory status and nociception in tongue sections, mainly from the tongue body. Technically, we found superiority of paraffin sections for collagen I, collagen III, fibronectin, ki67 and α-SMA labelling, for selected detections systems. As for ECM components, the lamina propria was very rich in collagen and fibronectin, while the muscular body of the tongue showed only collagen and fibronectin positive areas between the muscle fibers. Moreover, α-SMA was clearly expressed in the walls of arteries and veins. The inflammatory marker PAR-2 on the other hand was prominently expressed in the salivary glands and to some extent in the walls of the vessels. Particular PAR-2 expression was found in the excretory ducts of the tongue. This technical note has the aim to provide baseline images that can be used to compare the pathological state of the diseased rabbit tongue as well as for inter-species comparison, such as mouse or rat tongue. Finally, it can be used for the comparison with the human situation.
MeSH term(s)	Humans ; Rabbits ; Animals ; Rats ; Mice ; Immunohistochemistry ; Fibronectins/metabolism ; Ki-67 Antigen/metabolism ; Tongue/pathology ; Collagen/metabolism ; Formaldehyde
Chemical Substances	Fibronectins ; Ki-67 Antigen ; Collagen (9007-34-5) ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2023-11-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2023.152127
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Article ; Online: In Vitro Assessment of Bacterial Adhesion and Biofilm Formation on Novel Bioactive, Biodegradable Electrospun Fiber Meshes Intended to Support Tendon Rupture Repair.

Miescher, Iris / Rieber, Julia / Schweizer, Tiziano A / Orlietti, Mariano / Tarnutzer, Andrea / Andreoni, Federica / Meier Buergisser, Gabriella / Giovanoli, Pietro / Calcagni, Maurizio / Snedeker, Jess G / Zinkernagel, Annelies S / Buschmann, Johanna

ACS applied materials & interfaces

2024 Volume 16, Issue 5, Page(s) 6348–6355

Abstract: The surgical repair of a ruptured tendon faces two major problems: specifically increased fibrous adhesion to the surrounding tissue and inferior mechanical properties of the scar tissue compared to the native tissue. Bacterial attachment to implant ... ...

Abstract	The surgical repair of a ruptured tendon faces two major problems: specifically increased fibrous adhesion to the surrounding tissue and inferior mechanical properties of the scar tissue compared to the native tissue. Bacterial attachment to implant materials is an additional problem as it might lead to severe infections and impaired recovery. To counteract adhesion formation, two novel implant materials were fabricated by electrospinning, namely, a random fiber mesh containing hyaluronic acid (HA) and poly(ethylene oxide) (PEO) in a ratio of 1:1 (HA/PEO 1:1) and 1:4 (HA/PEO 1:4), respectively. Electrospun DegraPol (DP) treated with silver nanoparticles (DP-Ag) was developed to counteract the bacterial attachment. The three novel materials were compared to the previously described DP and DP with incorporated insulin-like growth factor-1 (DP-IGF-1), two implant materials that were also designed to improve tendon repair. To test whether the materials are prone to bacterial adhesion and biofilm formation, we assessed 10 strains of
MeSH term(s)	Humans ; Bacterial Adhesion ; Silver/pharmacology ; Silver/chemistry ; Insulin-Like Growth Factor I/pharmacology ; Metal Nanoparticles/chemistry ; Tendon Injuries/surgery ; Anti-Bacterial Agents/pharmacology ; Biofilms ; Tendons
Chemical Substances	Silver (3M4G523W1G) ; Insulin-Like Growth Factor I (67763-96-6) ; Anti-Bacterial Agents
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c15710
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Article ; Online: Supporting Cell-Based Tendon Therapy: Effect of PDGF-BB and Ascorbic Acid on Rabbit Achilles Tenocytes in Vitro.

Evrova, Olivera / Kellenberger, Damian / Calcagni, Maurizio / Vogel, Viola / Buschmann, Johanna

International journal of molecular sciences

2020 Volume 21, Issue 2

Abstract: Cell-based tendon therapies with tenocytes as a cell source need effective tenocyte in vitro expansion before application for tendinopathies and tendon injuries. Supplementation of tenocyte culture with biomolecules that can boost proliferation and ... ...

Abstract	Cell-based tendon therapies with tenocytes as a cell source need effective tenocyte in vitro expansion before application for tendinopathies and tendon injuries. Supplementation of tenocyte culture with biomolecules that can boost proliferation and matrix synthesis is one viable option for supporting cell expansion. In this in vitro study, the impacts of ascorbic acid or PDGF-BB supplementation on rabbit Achilles tenocyte culture were studied. Namely, cell proliferation, changes in gene expression of several ECM and tendon markers (collagen I, collagen III, fibronectin, aggrecan, biglycan, decorin, ki67, tenascin-C, tenomodulin, Mohawk, α-SMA, MMP-2, MMP-9, TIMP1, and TIMP2) and ECM deposition (collagen I and fibronectin) were assessed. Ascorbic acid and PDGF-BB enhanced tenocyte proliferation, while ascorbic acid significantly accelerated the deposition of collagen I. Both biomolecules led to different changes in the gene expression profile of the cultured tenocytes, where upregulation of collagen I, Mohawk, decorin, MMP-2, and TIMP-2 was observed with ascorbic acid, while these markers were downregulated by PDGF-BB supplementation. Vice versa, there was an upregulation of fibronectin, biglycan and tenascin-C by PDGF-BB supplementation, while ascorbic acid led to a downregulation of these markers. However, both biomolecules are promising candidates for improving and accelerating the in vitro expansion of tenocytes, which is vital for various tendon tissue engineering approaches or cell-based tendon therapy.
MeSH term(s)	Achilles Tendon/cytology ; Achilles Tendon/drug effects ; Animals ; Ascorbic Acid/pharmacology ; Becaplermin/pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Collagen ; Fibronectins ; Gene Expression/drug effects ; Humans ; Rabbits ; Tendon Injuries/drug therapy ; Tendon Injuries/genetics ; Tenocytes/cytology ; Tenocytes/drug effects ; Tissue Engineering ; Transcriptome
Chemical Substances	Fibronectins ; Becaplermin (1B56C968OA) ; Collagen (9007-34-5) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2020-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21020458
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